Glutathione is required for nitric oxide-induced chilling tolerance by synergistically regulating antioxidant system, polyamine synthesis, and mitochondrial function in cucumber (Cucumis sativus L.).

In this paper, we discussed the physiological mechanism of enhanced chilling tolerance with combined treatment of nitric oxide (NO) and reduced glutathione (GSH) in cucumber seedlings. With prolonged low temperature (10 °C/6 °C), oxidative stress improved, which was manifested as an increase the hydrogen peroxide (H2O2) and malondialdehyde (MDA), causing cell membrane damage, particularly after 48 h of chilling stress. Exogenous sodium nitroprusside (SNP, NO donor) enhanced the activity of nitric oxide synthase NOS-like, the contents of GSH and polyamines (PAs), and the cellular redox state, thus regulating the activities of mitochondrial oxidative phosphorylation components (CI, CII, CIV, CV). However, buthionine sulfoximine (BSO, a GSH synthase inhibitor) treatment drastically reversed or attenuated the effects of NO. Importantly, the combination of SNP and GSH treatment had the best effect in alleviating chilling-induced oxidative stress by upregulating the activities of antioxidant enzyme, including superoxidase dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and peroxidase (POD) and improved the PAs content, thereby increased activities of CI, CII, CIII, CIV, and CV. This potentially contributes to the maintenance of oxidative phosphorylation originating from mitochondria. In addition, the high activity of S-nitrosoglutathione reductase (GSNOR) in the combined treatment of SNP and GSH possibly mediates the conversion of NO and GSH to S-nitrosoglutathione. Our study revealed that the combined treatment with NO and GSH to synergistically improve the cold tolerance of cucumber seedlings under prolonged low-temperature stress.

The first structure of human Golm1 coiled coil domain reveals an unexpected tetramer and highlights its structural diversity.

Golgi membrane protein 1 (Golm1), a transmembrane protein with diverse subcellular localizations, has garnered significant attention in recent years due to its strong association with the development and progression of liver diseases and numerous cancers. Interestingly, although Golm1 is a membrane protein, the C-terminal of Golm1, which contains a coiled coil domain and a flexible acid region, can also be detected in the plasma of patients with various liver diseases. Notably, the coiled coil domain of serum Golm1 is postulated to play a pivotal role in physiological and pathological functions. However, little is currently known about the structure of this coiled coil domain and the full-length protein, which may limit our understanding of Golm1. Therefore, this study aims to address this gap in knowledge and reports the first crystal structure of the coiled coil domain of Golm1 at a resolution of 2.28 Å. Meanwhile, we have also confirmed that the Golm1 coiled coil domain in solution can form tetramer. Our results reveal that Golm1 can form a novel tetrameric structure that differs from the previous reported dimeric structure Golm1 could assemble, which may provide novel insights into the diversity of physiological functions and pathological roles.

The benefit of dupilumab as a postoperative short-term adjuvant therapy for chronic rhinosinusitis with nasal polyps: A preliminary study.

Introduction: Recent evidence recommends the use of biologics in patients with severe uncontrolled type 2 chronic rhinosinusitis with nasal polyp (CRSwNP) owing to its propensity for recurrence after functional endoscopic sinus surgery (FESS). Among the type 2 biologics used for the treatment of nasal polyps, dupilumab (Dupi, anti-IL-4) exhibited superior efficacy and safety in indirect comparison studies. Objective: This study aimed to evaluate the objective and subjective outcomes of patients with CRSwNP treated with and without adjuvant Dupi therapy after FESS. Methods: Adult patients with type 2 CRSwNP who underwent FESS with adjuvant Dupi after surgery were enrolled. A matched control group without adjuvant Dupi therapy were recruited during the same period. All patients underwent nasal endoscopy and completed the sinonasal outcome test-22 questionnaire evaluations at baseline and 3 months after surgery. Results: A total of 10 patients who received postoperative adjuvant therapy with Dupi and 20 patients who underwent surgery only were included. Patients with add-on Dupi therapy had significantly higher eosinophil cationic protein levels in the serum, eosinophil counts in peripheral blood, prevalence of asthma, and nasal polyp score at baseline. Both treatments were effective in reducing the patient's symptoms by SNOT-22 at 3 months postoperatively. However, patients with adjuvant Dupi therapy exhibited significantly better endoscopic scores than those with surgery only (p = .022). Conclusion: Surgery plays an important role in treating patients with CRSwNP, and adjuvant Dupi use may facilitate objective mucosal recovery postoperatively. Level of Evidence: 4.

Sex differences in the association of long-term exposure to heat stress on kidney function in a large Taiwanese population study.

The incidence and prevalence of dialysis in Taiwan are high compared to other regions. Consequently, mitigating chronic kidney disease (CKD) and the worsening of kidney function have emerged as critical healthcare priorities in Taiwan. Heat stress is known to be a significant risk factor for CKD and kidney function impairment. However, differences in the impact of heat stress between males and females remains unexplored. We conducted this retrospective cross-sectional analysis using data from the Taiwan Biobank (TWB), incorporating records of the wet bulb globe temperature (WBGT) during midday (11 AM-2 PM) and working hours (8 AM-5 PM) periods based on the participants' residential address. Average 1-, 3-, and 5-year WBGT values prior to the survey year were calculated and analyzed using a geospatial artificial intelligence-based ensemble mixed spatial model, covering the period from 2010 to 2020. A total of 114,483 participants from the TWB were included in this study, of whom 35.9% were male and 1053 had impaired kidney function (defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2). Multivariable analysis revealed that in the male participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were significantly positively associated with eGFR < 60 ml/min/1.73 m2 (odds ratio [OR], 1.096, 95% confidence interval [CI] = 1.002-1.199, p = 0.044 for 1 year; OR, 1.093, 95% CI = 1.000-1.196, p = 0.005 for 3 years; OR, 1.094, 95% CI = 1.002-1.195, p = 0.045 for 5 years). However, significant associations were not found for the working hours period. In the female participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.872, 95% CI = 0.778-0.976, p = 0.018 for 1 year; OR, 0.874, 95% CI = 0.780-0.978, p = 0.019 for 3 years; OR, 0.875, 95% CI = 0.784-0.977, p = 0.018 for 5 years). In addition, during the working hours period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were also significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.856, 95% CI = 0.774-0.946, p = 0.002 for 1 year; OR, 0.856, 95% CI = 0.774-0.948, p = 0.003 for 3 years; OR, 0.853, 95% CI = 0.772-0.943, p = 0.002 for 5 years). In conclusion, our results revealed that increased WBGT was associated with impaired kidney function in males, whereas increased WBGT was associated with a protective effect against impaired kidney function in females. Further studies are needed to elucidate the exact mechanisms underlying these sex-specific differences.

Sex difference in the associations among hyperuricemia with self-reported peptic ulcer disease in a large Taiwanese population study.

Background: Hyperuricemia may play a role in various systemic diseases. However, few studies have investigated the relationship between hyperuricemia and the risk of peptic ulcer disease (PUD). Therefore, in this population-based study, we enrolled over 120,000 participants from the Taiwan Biobank (TWB) and examined the risk factors for self-reported PUD. In addition, we investigated sex differences in the association between hyperuricemia and self-reported PUD. Methods: Data of 121,583 participants were obtained from the TWB. Male participants with a serum uric acid level >7 mg/dl and female participants with a serum uric acid level >6 mg/dl were classified as having hyperuricemia. Details of self-reported PUD were obtained by questionnaire. The association between hyperuricemia and self-reported PUD in the male and female participants was examined using multivariable logistic regression analysis. Results: The overall prevalence of self-reported PUD was 14.6%, with a higher incidence in males (16.5%) compared to females (13.5%). After multivariable adjustment, male sex [vs. female sex; odds ratio (OR) = 1.139; 95% confidence interval (CI) = 1.084-1.198; p < 0.001], and hyperuricemia (OR = 0.919; 95% CI = 0.879-0.961; p < 0.001) were significantly associated with self-reported PUD. Further, a significant interaction was found between sex and hyperuricemia on self-reported PUD (p = 0.004). Hyperuricemia was associated with a low risk of self-reported PUD in males (OR = 0.890; 95% CI = 0.837-0.947; p < 0.001) but not in females (p = 0.139). Conclusion: The prevalence of self-reported PUD was higher in the male participants than in the female participants. Hyperuricemia was associated with low prevalence of self-reported PUD in males, but not in females. Further studies are needed to clarify the mechanisms behind these observations and verify the potential protective role of hyperuricemia on the development of self-reported PUD.

The distinct and potentially conflicting effects of tDCS and tRNS on brain connectivity, cortical inhibition, and visuospatial memory.

Noninvasive brain stimulation (NIBS) techniques, including transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS), are emerging as promising tools for enhancing cognitive functions by modulating brain activity and enhancing cognitive functions. Despite their potential, the specific and combined effects of tDCS and tRNS on brain functions, especially regarding functional connectivity, cortical inhibition, and memory performance, are not well-understood. This study aims to explore the distinct and combined impacts of tDCS and tRNS on these neural and cognitive parameters. Using a within-subject design, ten participants underwent four stimulation conditions: sham, tDCS, tRNS, and combined tDCS + tRNS. We assessed the impact on resting-state functional connectivity, cortical inhibition via Cortical Silent Period (CSP), and visuospatial memory performance using the Corsi Block-tapping Test (CBT). Our results indicate that while tDCS appears to induce brain lateralization, tRNS has more generalized and dispersive effects. Interestingly, the combined application of tDCS and tRNS did not amplify these effects but rather suggested a non-synergistic interaction, possibly due to divergent mechanistic pathways, as observed across fMRI, CSP, and CBT measures. These findings illuminate the complex interplay between tDCS and tRNS, highlighting their non-additive effects when used concurrently and underscoring the necessity for further research to optimize their application for cognitive enhancement.

Factors influencing recurrence and model development for recurrence of minimally invasive percutaneous transhepatic lithotripsy: a single-center retrospective study.

OBJECTIVE: To identify factors influencing recurrence after percutaneous transhepatic choledochoscopic lithotripsy (PTCSL) and to develop a predictive model. METHODS: We retrospectively analyzed clinical data from 354 patients with intrahepatic and extrahepatic bile duct stones treated with PTCSL at Qinzhou First People's Hospital between February 2018 and January 2020. Patients were followed for three years and categorized into non-recurrence and recurrence groups based on postoperative outcome. Univariate analysis identified possible predictors of stone recurrence. Data were split using the gradient boosting machine (GBM) algorithm, assigning 70% as the training set and 30% as the test set. The predictive performance of the GBM model was assessed using the receiver operating characteristic (ROC) curve and calibration curve, and compared with a logistic regression model. RESULTS: Six factors were identified as significant predictors of recurrence: age, diabetes, total bilirubin, biliary stricture, number of stones, and stone diameter. The GBM model, developed based on these factors, showed high predictive accuracy. The area under the ROC curve (AUC) was 0.763 (95% CI: 0.695-0.830) for the training set and 0.709 (95% CI: 0.596-0.822) for the test set. Optimal cutoff values were 0.286 and 0.264, with sensitivities of 62.30% and 66.70%, and specificities of 77.20% and 68.50%, respectively. Calibration curves indicated good agreement between predicted probabilities and observed recurrence rates in both sets. DeLong's test revealed no significant differences between the GBM and logistic regression models in predictive performance (training set: D = 0.003, P = 0.997 > 0.05; test set: D = 0.075, P = 0.940 > 0.05). CONCLUSION: Biliary stricture, stone diameter, diabetes, stone number, age, and total bilirubin significantly influence stone recurrence after PTCSL. The GBM model, based on these factors, demonstrates robust accuracy and discrimination. Both GBM and logistic regression models effectively predicted stone recurrence post-PTCSL.

Cerebellar atrophy in genetic epileptic encephalopathies: A cohort study and a systematic review.

OBJECTIVE: To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs). METHODS: This research included a retrospective cohort study conducted from January 2016 to December 2023 and a systematic review on cerebellar atrophy in genetic EEs. Pediatric individuals who were diagnosed with EEs based on electroclinical features, carried causative gene variants, and exhibited cerebellar atrophy were recruited. Electroclinical features, neuroimaging findings, and causative variants of eligible individuals were analyzed. RESULTS: The cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 6 of the 10 individuals (6/10; 60 %) exhibited cerebellar signs. Diagnostic delay between the detection of cerebellar atrophy and the identification of genetic diagnosis existed in 6 individuals (6/10; 60 %) and the median duration was 4.4 years. A total of 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. Twenty-six genes (26/32; 81 %) accounted for cerebellar atrophy associated with other brain anomalies and 6 genes (6/32; 19 %) caused isolated cerebellar atrophy. Twenty-five genes (25/32; 78 %) showed late-onset cerebellar atrophy identified after the age of 1 year old. CONCLUSION: Cerebellar atrophy is not uncommon in genetic EEs and may serve as an indicator for molecular diagnosis in clinical practice. To shorten the diagnostic delay, follow-up neuroimaging study is crucial because of high rate of clinico-radiological dissociation and late-onset cerebellar atrophy in this patient group.

Effect of Kinesiology Taping on Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: The objective of this systematic review and meta-analysis was to evaluate the impact of kinesiology taping on individuals suffering from breast cancer-related lymphedema. METHODS AND METHODS: We conducted a comprehensive search in PubMed, Cochrane Library, and Embase databases, spanning from their inception date to December 20, 2023, to identify pertinent studies. Inclusion criteria comprised studies that (1) enrolled participants diagnosed with breast cancer-related lymphedema; (2) implemented kinesiology taping as the intervention; (3) incorporated either complete decongestive therapy, exercise, or sham taping as the control treatment; and (4) included clinical measurements such as the severity of lymphedema, upper limb function assessment, quality of life, and perceived comfort. RESULTS: Information was extracted from 14 randomized controlled trials (RCTs). The analyses demonstrated statistically significant improvement, indicating a preference for kinesiology taping in the outcomes of upper limb functional assessment (standardized mean difference [SMD] = -0.88, 95% confidence interval [CI]: [-1.22, -0.55]), quality of life (SMD = 0.50, 95% CI: [0.16, 0.84]), and perceived comfort (SMD = 0.85, 95% CI: [0.34, 1.36]). CONCLUSION: The findings suggest that kinesiology taping could be considered a viable option for individuals dealing with breast cancer-related lymphedema. Nevertheless, acknowledging certain limitations within this study, further confirmation of its benefits necessitates additional larger-scale and better-designed RCTs.

Sex difference in the associations among secondhand smoke with metabolic syndrome in non-smokers in a large Taiwanese population follow-up study.

Close associations among secondhand smoke (SHS) and metabolic syndrome (MetS) and its components have been demonstrated, however sex differences in these associations remain unclear. We collected 121,364 participants from the Taiwan Biobank, and excluded those with smoking history, the remaining 88,297 participants (male: 18,595; female: 69,702; mean age 50.1 ± 11.0 years) were included. SHS exposure was evaluated based on self-reported questionnaires. SHS was associated with MetS (odds ratio [OR], 1.268, p < 0.001 for males vs. 1.180, p < 0.001 for females), abdominal obesity (OR, 1.234, p < 0.001 for males vs. 1.199, p < 0.001 for females), low high-density lipoprotein cholesterol (OR, 1.183, p = 0.008 for males vs. 1.094, p = 0.011 for females), hyperglycemia (OR, 1.286, p < 0.001 for males vs. 1.234, p < 0.001 for females), but not with hypertriglyceridemia. SHS was associated with high blood pressure (BP) (OR, 1.278, p < 0.001) only in males, but not in females. Furthermore, significant interactions were found between sex x SHS on MetS (p = 0.023), abdominal obesity (p = 0.032), and elevated BP (p < 0.001). Moreover, the participants who were exposed to SHS for ≥1 hour per week were associated with a higher risk (OR = 1.316, p = 0.001 in males vs. OR = 1.220, p < 0.001 in females) of MetS compared to those with no exposure. These results showed an association between SHS and a high OR for MetS in both the males and females. Furthermore, sex differences were identified in the associations between SHS and MetS and its components, and SHS was more closely related to MetS, abdominal obesity, and high BP in males than in females.

Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer.

BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. METHODS: A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. RESULTS: In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. CONCLUSIONS: Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.

Exploring the novel benefits of leucine: Protecting nitrite-induced liver damage in sub-adult grass carp (Ctenopharyngodon idella) through regulating mitochondria quality control.

Leucine is an essential amino acid for fish. The ability of leucine to resist stress in fish has not been reported. Nitrite is a common pollutant in the aquatic environment. Therefore, we investigated the effects of dietary leucine on growth performance and nitrite-induced liver damage, mitochondrial dysfunction, autophagy, and apoptosis for sub-adult grass carp. A total of 450 grass carp (615.91 ± 1.15 g) were selected and randomly placed into 18 net cages. The leucine contents of the six diets were 2.91, 5.90, 8.92, 11.91, 14.93, and 17.92 g/kg, respectively. After a 9-week feeding trial, the nitrite exposure experiment was set up for 96 h. These results indicated that dietary leucine significantly promoted FW, WG, PWG, and SGR of sub-adult grass carp (P < 0.05). Appropriate levels of dietary leucine (11.91-17.92 g/kg) decreased the activities of serum parameters (glucose, cortisol, and methemoglobin contents, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase), the contents of reactive oxygen species (ROS), nitric oxide (NO) and peroxynitrite (ONOO-). In addition, appropriate levels of dietary leucine (11.91-17.92 g/kg) increased the mRNA levels of mitochondrial biogenesis genes (PGC-1α, Nrf1/2, TFAM), fusion-related genes (Opa1, Mfn1/2) (P < 0.05), and decreased the mRNA levels of caspase 3, caspase 8, caspase 9, fission-related gene (Drp1), mitophagy-related genes (Pink1, Parkin) and autophagy-related genes (Beclin1, Ulk1, Atg5, Atg7, Atg12) (P < 0.05). Appropriate levels of dietary leucine (8.92-17.92 g/kg) also increased the protein levels of AMP-activated protein kinase (AMPK), prostacyclin (p62) and decreased the protein levels of protein light chain 3 (LC3), E3 ubiquitin ligase (Parkin), and Cytochrome c (Cytc). Appropriate levels of leucine (8.92-17.92 g/kg) could promote growth performance and alleviate nitrite-induced mitochondrial dysfunction, autophagy, apoptosis for sub-adult grass carp. Based on quadratic regression analysis of PWG and serum GPT activity, dietary leucine requirements of sub-adult grass carp were recommended to be 12.47 g/kg diet and 12.55 g/kg diet, respectively.

A preliminary study of the effectiveness of video visitation on depression and stress in mothers with preterm infants during the pandemic.

BACKGROUND AND PURPOSE: Parents of preterm infants experience anxiety and stress in the neonatal intensive care unit (NICU). Visitation restrictions due to COVID-19 have increased maternal pressure and limited bonding opportunities. Little research exists in Taiwan on using video conferencing as a solution. This study investigates depression and stress levels in mothers of preterm infants and evaluates the effectiveness of video visitation during NICU restrictions. METHODS: This study adopts a cross-sectional design and a qualitative survey. Mothers of premature infants were recruited and they participated in the study. Interventions for video visits were scheduled on the third day of admission to the NICU (T1) and during the second week of the study (T2). After each video visit, participants completed an online survey. The study's online survey used structured questionnaires including demographics, the Edinburgh Postnatal Depression Scale (EPDS) and the Parental Stress Scale (PSS): Infant Hospitalization (IH). RESULTS: A total of 51 mothers of preterm infants participated in the study. During the T1 and T2 periods, single mothers with lower educational levels and those aged below 30 experienced depression and high levels of stress. Lower birth weight and gestational age were associated with maternal depression. Video visitation intervention led to a significant decrease in depression scores (EPDS, T1: 11.3 ± 5.5 vs. T2: 10.1 ± 5.2, p = 0.039). Positive correlations were observed between EPDS and PSS: IH scores (p < 0 .005). CONCLUSION: Video visitation intervention can reduce maternal depression in mothers with preterm infants. Since it is practical, video visitation may be applied even after the pandemic.

The prevalence of overt, occult, and no-demonstrated stress urinary incontinence and their clinical and urodynamic findings in women with advanced-stage cystoceles.

OBJECTIVES: To elucidate the prevalence of overt, occult and no demonstrated (ND) stress urinary incontinence (SUI) in women with advanced-stage cystoceles. STUDY DESIGN: Between November 2011 and January 2017, all women with ≥stage 2 cystoceles were retrospectively enrolled. Overt SUI was diagnosed before the prolapse reduction test, and occult SUI was diagnosed when urine leakage was noted after a reduction test with vaginal gauze. Otherwise, a diagnosis of ND-SUI was made. MAIN OUTCOME MEASURES: The prevalence, clinical and urodynamic findings of overt SUI, occult SUI, and ND-SUI. RESULTS: In 480 enrolled women, 62% had overt SUI, 17% had occult SUI, and 21% had ND-SUI. The occult SUI group had the most advanced prolapse. The pad weight results after prolapse reduction (37.3 ± 44.3 vs. 13.4 ± 21.9, p < 0.05), the bladder capacity (243 ± 54 vs. 273 ± 48, p < 0.001), and questionnaires regarding life quality were significantly different between the overt SUI and the occult SUI groups. Bladder oversensitivity (BO) was the most common urodynamic diagnosis (389/480, 81%), especially in overt SUI, while urodynamic stress incontinence (56/480, 12%) and detrusor overactivity (60/480, 13%) were uncommon. The cutoff value of stage 3 uterine prolapse was the strongest predictor for predicting occult SUI (sensitivity = 30.3%, specificity = 78.5%; area = 0.60, 95% CI: 0.52-0.68). CONCLUSIONS: SUI occurs in a ratio of 3:1:1 among cases with overt, occult, and no demonstrable symptoms. BO is the most common urodynamic diagnosis. Pad test with prolapse reduction remains an important tool, especially for coexistent stage 3 uterine prolapse.

Single-cell morphology encodes functional subtypes of senescence in aging human dermal fibroblasts.

Cellular senescence is an established driver of aging, exhibiting context-dependent phenotypes across multiple biological length-scales. Despite its mechanistic importance, profiling senescence within cell populations is challenging. This is in part due to the limitations of current biomarkers to robustly identify senescent cells across biological settings, and the heterogeneous, non-binary phenotypes exhibited by senescent cells. Using a panel of primary dermal fibroblasts, we combined live single-cell imaging, machine learning, multiple senescence induction conditions, and multiple protein-based senescence biomarkers to show the emergence of functional subtypes of senescence. Leveraging single-cell morphologies, we defined eleven distinct morphology clusters, with the abundance of cells in each cluster being dependent on the mode of senescence induction, the time post-induction, and the age of the donor. Of these eleven clusters, we identified three bona-fide senescence subtypes (C7, C10, C11), with C10 showing the strongest age-dependence across a cohort of fifty aging individuals. To determine the functional significance of these senescence subtypes, we profiled their responses to senotherapies, specifically focusing on Dasatinib + Quercetin (D+Q). Results indicated subtype-dependent responses, with senescent cells in C7 being most responsive to D+Q. Altogether, we provide a robust single-cell framework to identify and classify functional senescence subtypes with applications for next-generation senotherapy screens, and the potential to explain heterogeneous senescence phenotypes across biological settings based on the presence and abundance of distinct senescence subtypes.

Variations in touch representation in the hummingbird and zebra finch forebrain.

Somatosensation is essential for animals to perceive the external world through touch, allowing them to detect physical contact, temperature, pain, and body position. Studies on rodent vibrissae have highlighted the organization and processing in mammalian somatosensory pathways.1,2 Comparative research across vertebrates is vital for understanding evolutionary influences and ecological specialization on somatosensory systems. Birds, with their diverse morphologies, sensory abilities, and behaviors, serve as ideal models for investigating the evolution of somatosensation. Prior studies have uncovered tactile-responsive areas within the avian telencephalon, particularly in pigeons,3,4,5,6 parrots,7 and finches,8 but variations in somatosensory maps and responses across avian species are not fully understood. This study aims to explore somatotopic organization and neural coding in the telencephalon of Anna's hummingbirds (Calypte anna) and zebra finches (Taeniopygia guttata) by using in vivo extracellular electrophysiology to record activity in response to controlled tactile stimuli on various body regions. These findings reveal unique representations of body regions across distinct forebrain somatosensory nuclei, indicating significant differences in the extent of areas dedicated to certain body surfaces, which may correlate with their behavioral importance.

Reproducibility between preschool and school-age Social Responsiveness Scale forms in the Environmental influences on Child Health Outcomes program.

Evidence suggests core autism trait consistency in older children, but development of these traits is variable in early childhood. The Social Responsiveness Scale (SRS) measures autism-related traits and broader autism phenotype, with two age-dependent forms in childhood (preschool, 2.5-4.5 years; school age, 4-18 years). Score consistency has been observed within forms, though reliability across forms has not been evaluated. Using data from the Environmental Influences on Child Health Outcomes (ECHO) program (n = 853), preschool, and school-age SRS scores were collected via maternal report when children were an average of 3.0 and 5.8 years, respectively. We compared reproducibility of SRS total scores (T-scores) and agreement above a clinically meaningful cutoff (T-scores ≥ 60) and examined predictors of discordance in cutoff scores across forms. Participant scores across forms were similar (mean difference: 3.3 points; standard deviation: 7), though preschool scores were on average lower than school-age scores. Most children (88%) were classified below the cutoff on both forms, and overall concordance was high (92%). However, discordance was higher in cohorts following younger siblings of autistic children (16%). Proportions of children with an autism diagnoses were also higher among those with discordant scores (27%) than among those with concordant scores (4%). Our findings indicate SRS scores are broadly reproducible across preschool and school-age forms, particularly for capturing broader, nonclinical traits, but also suggest that greater variability of autism-related traits in preschool-age children may reduce reliability with later school-age scores for those in the clinical range.

Adaptation mechanism of three Impatiens species to different habitats based on stem morphology, lignin and MYB4 gene.

BACKGROUND: Impatiens is an important genus with rich species of garden plants, and its distribution is extremely extensive, which is reflected in its diverse ecological environment. However, the specific mechanisms of Impatiens' adaptation to various environments and the mechanism related to lignin remain unclear. RESULTS: Three representative Impatiens species,Impatiens chlorosepala (wet, low degree of lignification), Impatiens uliginosa (aquatic, moderate degree of lignification) and Impatiens rubrostriata (terrestrial, high degree of lignification), were selected and analyzed for their anatomical structures, lignin content and composition, and lignin-related gene expression. There are significant differences in anatomical parameters among the stems of three Impatiens species, and the anatomical structure is consistent with the determination results of lignin content. Furthermore, the thickness of the xylem and cell walls, as well as the ratio of cell wall thickness to stem diameter have a strong correlation with lignin content. The anatomical structure and degree of lignification in Impatiens can be attributed to the plant's growth environment, morphology, and growth rate. Our analysis of lignin-related genes revealed a negative correlation between the MYB4 gene and lignin content. The MYB4 gene may control the lignin synthesis in Impatiens by controlling the structural genes involved in the lignin synthesis pathway, such as HCT, C3H, and COMT. Nonetheless, the regulation pathway differs between species of Impatiens. CONCLUSIONS: This study demonstrated consistency between the stem anatomy of Impatiens and the results obtained from lignin content and composition analyses. It is speculated that MYB4 negatively regulates the lignin synthesis in the stems of three Impatiens species by regulating the expression of structural genes, and its regulation mechanism appears to vary across different Impatiens species. This study analyses the variations among different Impatiens plants in diverse habitats, and can guide further molecular investigations of lignin biosynthesis in Impatiens.

PanIN or IPMN? Redefining Lesion Size in 3 Dimensions.

Pancreatic ductal adenocarcinoma (PDAC) develops from 2 known precursor lesions: a majority (∼85%) develops from pancreatic intraepithelial neoplasia (PanIN), and a minority develops from intraductal papillary mucinous neoplasms (IPMNs). Clinical classification of PanIN and IPMN relies on a combination of low-resolution, 3-dimensional (D) imaging (computed tomography, CT), and high-resolution, 2D imaging (histology). The definitions of PanIN and IPMN currently rely heavily on size. IPMNs are defined as macroscopic: generally >1.0 cm and visible in CT, and PanINs are defined as microscopic: generally <0.5 cm and not identifiable in CT. As 2D evaluation fails to take into account 3D structures, we hypothesized that this classification would fail in evaluation of high-resolution, 3D images. To characterize the size and prevalence of PanINs in 3D, 47 thick slabs of pancreas were harvested from grossly normal areas of pancreatic resections, excluding samples from individuals with a diagnosis of an IPMN. All patients but one underwent preoperative CT scans. Through construction of cellular resolution 3D maps, we identified >1400 ductal precursor lesions that met the 2D histologic size criteria of PanINs. We show that, when 3D space is considered, 25 of these lesions can be digitally sectioned to meet the 2D histologic size criterion of IPMN. Re-evaluation of the preoperative CT images of individuals found to possess these large precursor lesions showed that nearly half are visible on imaging. These findings demonstrate that the clinical classification of PanIN and IPMN fails in evaluation of high-resolution, 3D images, emphasizing the need for re-evaluation of classification guidelines that place significant weight on 2D assessment of 3D structures.